The ADRC at Columbia seeks to advance and disseminate knowledge of the causes, prevention and treatment of Alzheimer's Disease and other age-related dementing disorders. To do this, we maintain and follow a multi-ethnic and multi-racial patient population of normal elderly and the elderly with cognitive disorders to establish the natural history of the disease as a function of age and of genetic makeup. In this application we propose to use a variety of neuropsychological, neurological and imaging tools to examine the earliest stages of AD and to follow these subjects throughout their lives and to compare them to other dementing diseases. A comprehensive neuropathologic examination will be performed on the deceased participants correlated with the clinical, radiological and genetic data. Tissues and DNA obtained from these subjects will be available for research on the biology and genetics of the disease. Individual research projects within the ADRC will examine various aspects of the cellular and molecular biology of AD with emphasis on lipids, on retromer function and on the relationship of GBA mutations to dementia. Patients enrolled in the ADRC will have the opportunity to participate in trials of new drugs and treatments for dementing diseases as they become available. The well-documented cognitive status of these patients makes them highly suitable for inclusion in clinical trials. The Education and Information Core of the Columbia ADRC endeavors to educate both lay and medical communities about AD, about the latest advances in research and about the care of the AD patient. The ADRC serves as a resource for scientists with Columbia as well as outside of it, encouraging new research avenues by the award of pilot grants, by providing tissues and other biological samples, by providing access to a carefully documented patient population and by numerous seminars and Clinical Pathological Correlation Conferences. The Genetics Core serves as the major organizer of family recruitment and identification across the ADRCs and ADCs as well as resources for genotyping and gene expression studies. HIPAA compliant data organization and statistical consulting services are provided under the ADRC to the research community at Columbia and external to it.